- The phase 3 PARADIGMS trial showed superior efficacy of fingolimod over interferon beta-1a in reducing relapses in children and adolescents with multiple sclerosis who received treatment for a median of 1.61 years
- The relapse rate with fingolimod was similar to those seen in phase 3 trials of fingolimod in adults
- The annualized rate of new or newly enlarged lesions, the key secondary end point, was significantly lower with fingolimod than with interferon beta-1a
In May 2018, the Food and Drug Administration (FDA) expanded the approval of fingolimod, an oral treatment for relapsing forms of multiple sclerosis (MS), to include children ages 10 and older. This was the first FDA approval of a drug to treat MS in pediatric patients.
Tanuja Chitnis, MD, director of the Partners Pediatric Multiple Sclerosis Center, was a lead investigator in the international PARADIGMS phase 3 trial of fingolimod, which formed the basis of the expanded FDA approval. Details of the study results are available in the New England Journal of Medicine.
PARADIGMS compared fingolimod with interferon beta-1a in patients with relapsing MS who were 10 to 17 years of age. Altogether, 215 patients were enrolled at 80 centers in 25 countries.
Key eligibility criteria were:
- At least one relapse of multiple sclerosis in the past year, at least two relapses in the past two years or at least one gadolinium-enhancing lesion on magnetic resonance imaging in the six months before randomization
- A score of 0 to 5.5 on the Expanded Disability Status Scale
Eligible patients were randomly assigned to one of the following regimens for up to 24 months:
- Oral fingolimod (0.5 mg once daily, or 0.25 mg once daily for body weight ≤40 kg) plus a placebo-prefilled syringe for intramuscular injection
- Intramuscular interferon beta-1a (30 mcg once weekly) plus placebo capsule
Primary End Point
The adjusted annualized relapse rate, the primary endpoint, was 0.12 with fingolimod and 0.67 with interferon beta-1a. The investigators note that the relapse rate with fingolimod is similar to those observed in phase 3 trials of fingolimod in adults.
Key Secondary End Point
The annualized rate of new or newly enlarged lesions, the key secondary endpoint, was 4.39 with fingolimod and 9.27 with interferon beta-1a.
Other Secondary End Points
The percentage of patients free of relapse at month 24 was 85.7% with fingolimod and 38.8% with interferon beta-1a (difference, 46.9 percentage points; unadjusted 95% CI, 33.7–60.1).
The median time to first confirmed relapse was more than 720 days with fingolimod and 488 days with interferon beta-1a (hazard ratio, 0.18; 95% CI, 0.10–0.32; < .001).
The mean number of gadolinium-enhancing lesions per scan at up to 24 months was 0.44 with fingolimod and 1.28 with interferon beta-1a (rate ratio, 0.34; unadjusted 95% CI, 0.22–0.54).
The median duration of treatment was 634 days in the fingolimod group and 547 days in the interferon beta-1a group (overall median of 1.61 years).
Adverse events leading to discontinuation of the trial regimen occurred in 4.7% of the fingolimod group and 2.8% of the interferon group. Serious adverse events occurred in 16.8% and 6.5%, respectively.
Serious adverse events in the fingolimod group included:
- Six cases of convulsions (5.6%, compared with 0.9% in the interferon beta-1a group)
- Two cases of leukopenia (1.9%)
- One case each of a number of other conditions
No opportunistic infections or cancers were reported in either group, and there were no deaths during the trial period.
To gain more information about the safety and durability of fingolimod, the investigators are currently conducting an open-label five-year extension trial with the same patients.
Learn more about the Partners Pediatric Multiple Sclerosis Center
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